US3925165A - Apparatus for culturing of tissue cells and micro-organisms - Google Patents

Apparatus for culturing of tissue cells and micro-organisms Download PDF

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Publication number
US3925165A
US3925165A US388036A US38803673A US3925165A US 3925165 A US3925165 A US 3925165A US 388036 A US388036 A US 388036A US 38803673 A US38803673 A US 38803673A US 3925165 A US3925165 A US 3925165A
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Prior art keywords
carriers
support
axis
housing
combination
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US388036A
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English (en)
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Hans Muller
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Chemap AG
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/06—Plates; Walls; Drawers; Multilayer plates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/14—Rotation or movement of the cells support, e.g. rotated hollow fibers

Definitions

  • ABSTRACT A rotatable shaft is mounted in a housing and a plurality of culture carriers having exposed surfaces on which the respective cultures are to grow, is releasably connected with the support to extend radially from the same within the housing. A drive is provided for rotating the support or shaft.
  • FIG. 3B I APPARATUS FOR CULTURING OF TISSUE CELLS AND MICRO-ORGANISMS BACKGROUND OF THE INVENTION
  • the present invention relates to an apparatus for culturing of tissue cells and micro-organisms in general, and more particularly to an apparatus of this type wherein the carriers on which the cultures are to be grown, can be rotated.
  • Apparatus of this type is already known in the art.
  • an apparatus having a plurality of plates which are arranged one above the other and on which the culture medium is to be grown.
  • an improved type of apparatus has been proposed, which is not only more effective but also smaller than those known from the previous art, wherein the carrier is configurated as a spiral element of synthetic plastic material, enamelled metal or glass. These materials have been found to be the most advantageous for the growth of cultures.
  • the circumferential length of the strip may be shorter but in that case its width (its dimension in axial length of the spiral) will be greater.
  • these spiral carriers are then very diffic ult to clean, and can in fact be cleaned (for subsequent removal of the tissue cells or micro-organisms when the particular culturing operation is completed) only with the aid of complicated and expensive auxiliary equipment.
  • Even the use of granular cleaning aids, which are intended to scour the cells or micro-organisms off the surfaces of the spiral carrier when admitted into the housing while the spiral carrier is rotated at a fast speed, does not provide for a completely effective cleaning action.
  • Another object of the invention is to provide such an improved apparatus which affords the advantages of the type of apparatus outlined earlier and having a spiral carrier, but which provides for a better gas exchange per unit of time.
  • Another object of the invention is to provide such an improved apparatus which facilitates greatly the cleaning of the culture carriers.
  • Another object of the invention is to provide an apparatus of the type in question, wherein the cleaning of the culture carriers with the aid of granular cleaning aids is particularly facilitated.
  • Still an additional object of the invention is to provide such an improved apparatus wherein the inspection of the culture carriers, which is necessary from time to time, is made much simpler than heretofore.
  • one feature of the invention resides in an apparatus for culturing of tissue cells and micro-organisms which, briefly stated, comprises a housing, a rotatable support mounted in the housing, and a plurality of culture carriers having exposed surfaces on which the respective cultures are to grow. Connecting means releasably connects the carriers with the support, and drive means serve to rotate the support.
  • FIG. I is a somewhat diagrammatic axial section through an apparatus according to the present invention.
  • FIG. 2 is a section taken on line Il-II of FIG. 1;
  • FIG. 3A is a plan view of one of the culture carriers in the apparatus of FIGS. 1 and 2;
  • FIG. 3B is an end view of the carrier in FIG. 3A, looking towards the right in that Figure;
  • FIG. 4 is a fragmentary section illustrating further details of the invention.
  • FIG. 5 is a fragmentary detail view, illustrating another embodiment of the invention.
  • the apparatus utilizes a cylindrical housing which in the illustrated embodiment is constituted by a cylinder 9 of glass or synthetic plastic material.
  • a cylindrical housing which in the illustrated embodiment is constituted by a cylinder 9 of glass or synthetic plastic material.
  • two end covers I l which are mounted on the cylinder 9 by means of longitudinally extending rods 10, onto free threaded ends of which there are threaded the illustrated nuts, so that the covers l I are pressed against the opposite open ends of the cylinder 9.
  • the inwardly directed sides of the covers 1 I are provided with annular grooves in which sealing material may be located as illustrated, so that the opposite ends of the cylinder 9 extend into these grooves and engage the sealing material, whereby the housing is sealed.
  • a support is provided in form of a hollow shaft 4 which extends axially through the housing and on which there are provided two axially spaced annuli of projections 17. Successive ones of the projections 17, that is circumferentially successive ones of them, define with one another narrow grooves or spaces.
  • the carriers for the culture to be grown are identified with reference numeral 1 and their inner longitudinal edges, that is those closest to the shaft 4, are received in these gaps or grooves. The insertion can be made axially or radially with respect to the shaft 4.
  • Each of the carriers I has two axially spaced ends, and adjacent the respective ends of the set of carriers 1 there are located end plates 19.
  • a sealing member 7 (here of disc-shaped configuration) between the respective end plate 19 and the juxtaposed ends of the carriers 1.
  • the carriers 1 will, incidentally, be seen to be circumferentially distributed about the periphery of the shaft 4 (see FIG. 2) and to be curved in the circumferential direction of the shaft 4.
  • the end plate 19 abuts a shoulder of the shaft 4, and at the right-hand end the end plate 19 is held in place by a nut 20 which is threaded onto threads provided for this purpose on the shaft 4.
  • the end plates 19 are pressed against the opposite axial ends of the carriers 1, holding the latter in position so that they cannot slip out of the respective grooves (note the axially extending annular flange on the outer periphery of each of the end plates 19).
  • the inner edges of the carriers I are not directly in contact with 4 the periphery of the shaft 4, but are slightly spaced from the same so that together they form an annular clearance C about the periphery of the shaft 4 (see FIG. 1), which clearance C of course communicates with the spaces between the circumferentially adjacent carriers 1.
  • the end plates 19 are each provided with apertures 3 which communicate with the clearance C and which also communicate with the interior of the hous-
  • the shaft 4 communicates via an inlet 12 with a source of heat exchange fluid (for heating or cooling purposes) which circulates through the shaft 4 and leaves the latter through the outlet 12'.
  • the shaft 4 is journalled at the left-hand end of FIG.
  • a seal 5 (of the type that can be maintained sterile, and which is well known from the art) through which it extends to the exterior of the housing.
  • Inlets 6 are provided for the admission of air and/or other gas into the interior of the housing, and a port 8 is provided through which nutrient medium can be admitted and through which it can also be discharged.
  • each of the carriers I is provided with at least one abutment 18 which in the illustrated embodiment is formed adjacent the radially outer edge of the respective carrier 1 and which abuts a circumferentially successive one of the carriers 1.
  • the components 4, l, 19 and 7 in effect constitute a rotatable drum which is located in the interior of the housing. This drum is a structural unit, not the least due to the fact that the axially extending annular flanges at the outer peripheries of the plates 19 hold the carriers 1 in place.
  • nutrient medium is admitted through the port 8 until it completely covers the shaft 4 so that the uppermost ones of the carriers 1 still extend out of the nutrient medium.
  • the drive composed of an electromotor 13, as well as drive belt 16 and the associated drive pulleys l4 and 15, is energized so that the shaft 4 begins to rotate very slowly, in the illustrated embodiment in clockwise direction.
  • Clockwise direction is assumed because in this embodiment the carriers 1 are curved in circumferential direction, and in particular in clockwise direction. During such rotation in clockwise direction the successive curved carriers 1 enter out of the upper space of the housing, which is not filled with nutrient medium, into the nutrient medium which is accommodated in the housing in the lower space thereof.
  • FIGS. 3A and 3B I have illustrated one of the carriers 1, in plan view and in end view, respectively. It will be seen how each of the carriers -1 is curved, without requiring a detailed description.
  • FIG. 4 shows on an enlarged scale how the carriers 1 are mounted there on the shaft 4, except that in this embodiment the projections 17 are replaced with grooves 170 which are formed in the outer periphery of the carrier 4 and extend in axial parallelism with the axis of rotation of the same.
  • FIG. 4 additionally shows that in place of the curved carriers 1, or in addition to them it is also possible to provide planar carriers la which can again be secured to the carrier 4 by means of the grooves 17a or as in FIGS. 1-3, by means of the projections 17.
  • FIG. 5 finally, illustrates an additional embodiment of the invention which shows that the shaft 4 can also be provided with more than one type of connecting means.
  • I have illustrated the projections 17 which were described with respect to FIGS. 1-3. It is also possible, however, to provide the grooves 170 (shown in FIG. 4, but not in FIG. 5) or the pin-shaped projections 21 which are shown in FIG. 5. The inner edges of the carriers 1 or In would be received between circumferentially adjacent ones of the projections 21, just as they can be received between circumferentially adjacent ones of the projections 17.
  • all three types of connecting means can be provided on one and the same shaft 4, if desired.
  • the apparatus according to the present invention meets all requirements made of it, as set forth in the introductory portions of this specification, and that it overcomes the disadvantages outlined with respect to the prior art.
  • the novel apparatus has further advantages, particularly with reference to the type of apparatus of the prior art which uses a spiral carrier, especially in terms of a simple and economically advantageous manufacture of such an apparatus. Because the individual carriers 1, if they are curved, are all of the same curvature, only a single apparatus is required for producing them if they are made of synthetic plastic or metal.
  • the apparatus according to the present invention assures that even during a slow rotation of the shaft 4 sufficient gas will come in contact with a relatively small surface 6 area carrying the growing culture, so that a more perfect gas exchange (contact of gas and growing culture per unit time) is obtained.
  • the fact that the carriers 1 or 1a can be readily removed facilities greatly their inspection and cleaning or replacement.
  • countries for instance, where it is required that when a job is completed with an apparatus of the type in question, the apparatus must be completely disassembled and cleaned, or where such a requirement is made after a certain number of production cycles has been completed.
  • this is very readily possible in the apparatus according to the present invention, because merely a removal of one of the plates 11 and one of the plates 19 will suffice to be able to withdraw the carriers 1 for inspection and cleaning.
  • the rather simple shape of the carriers 1 or 1a makes it possible to make them not only of synthetic plastic material or of metal, but also of glass. This is a material which in many instances is vastly preferred over any other type of material for culture growing because it has been found to be highly advantageous for this purpose, especially for the growing of monolayer cultures.
  • planar carriers 10 are of course particularly simple and inexpensive, especially if they are to be made of glass.
  • An apparatus according to the present invention can have a very large composite surface area on which to grow tissue cell cultures or micro-organisms, because more than one of the shafts 4 with the associated carriers 1 and other components can be accommodated in a single housing, or the housing can be made long enough and either the carriers 1 or 10 can be made very long or a plurality of sets of carriers 1 or In can be provided on the shafts 4 and at axially spaced locations thereof.
  • a combination comprising a housing; a support mounted in said housing for rotation about an axis; drive means for rotating said support about said axis; a plurality of elongated culture carriers circumferentially spaced from each other about the periphery of said support and each elongated in a direction parallel to said axis and partly bounding with an adjacent carrier a space that is elongated lengthwise of said axis, and having exposed surfaces on which respective cultures are to grow, and longitudinally spaced ends; connecting means for releasably connecting said carriers with said support; and a pair of end plates located at the respective ends of said carriers.
  • a combination comprising a housing; a support mounted in said housing for rotation about an axis; drive means for rotating said support about said axis; a plurality of elongated culture carriers circumferentially spaced from each other about the periphery of said support and each extending in a direction parallel to said axis and having exposed surfaces on which the respective cultures are to grow, and longitudinally spaced ends; connecting means for releasably connecting said carriers with said support and including first connecting portions on said support, and cooperating second connecting portions on said carriers and engaging said first connecting portions; and a pair of end plates located at and interposed between the respective ends of said carriers and the interior of said housing and holding said carriers in their respective positions relative to said support.
  • a combination comprising a housing; a support element mounted in said housing for rotation about an axis; drive means for rotating said support element about said axis; a plurality of elongated culture carrier elements circumferentially spaced from each other about the periphery of said support and each extending in a direction parallel to said axis and having exposed surfaces on which the respective cultures are to grow, and longitudinally spaced ends; connecting means for releasably connecting said carrier elements with said support element and including grooves on one of said elements and extending along said axis, and engaging portions on the other of said elements and received in the respective grooves; and a pair of end plates located at and interposed between the respective ends of said carrier elements and the interior of said housing and holding said carrier elements in their respective positions relative to said support elements.
  • said carriers are strip-shaped; and wherein said connecting 8 means comprises grooves formed in said support in substantial parallelism with the axis of rotation of the same, said carriers being partly received in respective ones of said grooves and projecting from the same in direction radially of said axis of rotation.
  • said connecting means comprises projections provided on said support and extending in substantial parallelism with the axis of rotation of the same, said projections being spaced circumferentially of said axis; and wherein said carriers each have a portion received between two circumferentially successive ones of said projections.
  • said support has grooves which extend in substantial parallelism with its axis of rotation; and wherein said carriers are of curved strip-shaped configuration and each have a marginal portion received in one of said grooves.
  • said connecting means comprises projections on said support, extending in substantial parallelism with the axis of rotation of the same and being spaced circumferentially of said axis; and wherein said carriers are of curved strip-shaped configuration and each have a portion received between two circumfere ntially successive ones of said projections.
  • said carriers each having an edge face adjacent to but slightly spaced from said periphery, so that all of said edge faces define about said periphery an annular gap which is in communication with the spaces between periphen ally adjacent ones of said carriers.
  • each abutment portion on each of said carriers intermediate said edges thereof, each abutment portion being in abutment with a circumferentially adjacent carrier so as to fix the circumferential distance between the carriers.

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  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Sustainable Development (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Immunology (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
US388036A 1972-08-18 1973-08-13 Apparatus for culturing of tissue cells and micro-organisms Expired - Lifetime US3925165A (en)

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CH1232672A CH563456A5 (US20030199744A1-20031023-C00003.png) 1972-08-18 1972-08-18

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CH (1) CH563456A5 (US20030199744A1-20031023-C00003.png)
DD (1) DD107484A5 (US20030199744A1-20031023-C00003.png)
FR (1) FR2196388B1 (US20030199744A1-20031023-C00003.png)
GB (1) GB1423218A (US20030199744A1-20031023-C00003.png)
IT (1) IT998367B (US20030199744A1-20031023-C00003.png)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4228242A (en) * 1977-08-16 1980-10-14 Chemap Ag Arrangement for cultivating cells of animal and human tissues
US4339537A (en) * 1978-11-10 1982-07-13 Olympus Optical Company Limited Method of culturing biological substances
US4376826A (en) * 1980-06-17 1983-03-15 Mynatt Roy L Continuous production of bacteria for leaching of metallic ore
US4379846A (en) * 1981-04-27 1983-04-12 Shkidchenko Alexandr N Fermentation apparatus
US4535062A (en) * 1982-02-12 1985-08-13 Chemap Ag Apparatus for growing microorganisms
DE3544382A1 (de) * 1985-12-14 1987-06-19 Ivan Prof Dr Ing Sekoulov Verfahren zur sauerstoffversorgung von bioreaktoren und vorrichtung zur durchfuehrung des verfahrens und die anwendung der vorrichtung
US5026650A (en) * 1988-06-30 1991-06-25 The United States Of Amercia As Represented By The Administrator Of The National Aeronautics And Space Administration Horizontally rotated cell culture system with a coaxial tubular oxygenator
US5081035A (en) * 1988-04-18 1992-01-14 The University Of Michigan Bioreactor system
US5316945A (en) * 1991-12-14 1994-05-31 Will Minuth Cell carrier arrangement
US5403742A (en) * 1993-09-01 1995-04-04 Ramot University Authority Ltd. Bioreactor for production of products with immobilized biofilm
US5427948A (en) * 1993-07-29 1995-06-27 Michigan State University Apparatus for conducting hybridization
US5432087A (en) * 1990-11-29 1995-07-11 Spielmann; Richard Apparatus having rotatable planar trays for culturing microorganisms
US5437998A (en) * 1993-09-09 1995-08-01 Synthecon, Inc. Gas permeable bioreactor and method of use
US5439823A (en) * 1993-09-01 1995-08-08 Martial Plant Corporation Apparatus for fast fermentation treatment
US5650325A (en) * 1990-11-29 1997-07-22 Spielmann; Richard Apparatus having a rotatable stack of parallel trays with culturing surfaces on opposite sides for liquid/gas exchange
US6001642A (en) * 1998-06-29 1999-12-14 Wyle Laboratories, Inc. Life Sciences Bioreactor and cell culturing processes using the bioreactor
US7198940B2 (en) 2000-10-25 2007-04-03 Shot Hardware Optimization Technology, Inc. Bioreactor apparatus and cell culturing system
US20090130757A1 (en) * 2005-10-26 2009-05-21 Terentiev Alexandre N Bioreactor with mixer and sparger
US20100015696A1 (en) * 2006-05-13 2010-01-21 Tom Claes Disposable bioreactor
US20100290308A1 (en) * 2000-10-09 2010-11-18 Terentiev Alexandre N Systems using a levitating, rotating pumping or mixing element and related methods

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102007003742A1 (de) * 2007-01-19 2008-07-24 Schmack Biogas Ag Rührwerk für Fermentationsbehälter
CN111518693A (zh) * 2020-04-30 2020-08-11 王家文 一种旋转式径向铺展轴向多片贴壁细胞培养器

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2996429A (en) * 1959-02-12 1961-08-15 Nat Toxicological Lab Inc Method and apparatus for growing living tissue
US3767535A (en) * 1971-06-14 1973-10-23 Corning Glass Works Method of reacting an insolubilized enzyme in a fluid medium
US3839155A (en) * 1972-07-27 1974-10-01 Merck & Co Inc Cell and vaccine production

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2996429A (en) * 1959-02-12 1961-08-15 Nat Toxicological Lab Inc Method and apparatus for growing living tissue
US3767535A (en) * 1971-06-14 1973-10-23 Corning Glass Works Method of reacting an insolubilized enzyme in a fluid medium
US3839155A (en) * 1972-07-27 1974-10-01 Merck & Co Inc Cell and vaccine production

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4228242A (en) * 1977-08-16 1980-10-14 Chemap Ag Arrangement for cultivating cells of animal and human tissues
US4310630A (en) * 1977-08-16 1982-01-12 Chemap Ag Arrangement for cultivating cells of animal and human tissues
US4339537A (en) * 1978-11-10 1982-07-13 Olympus Optical Company Limited Method of culturing biological substances
US4376826A (en) * 1980-06-17 1983-03-15 Mynatt Roy L Continuous production of bacteria for leaching of metallic ore
US4379846A (en) * 1981-04-27 1983-04-12 Shkidchenko Alexandr N Fermentation apparatus
US4535062A (en) * 1982-02-12 1985-08-13 Chemap Ag Apparatus for growing microorganisms
DE3544382A1 (de) * 1985-12-14 1987-06-19 Ivan Prof Dr Ing Sekoulov Verfahren zur sauerstoffversorgung von bioreaktoren und vorrichtung zur durchfuehrung des verfahrens und die anwendung der vorrichtung
US5081035A (en) * 1988-04-18 1992-01-14 The University Of Michigan Bioreactor system
US5026650A (en) * 1988-06-30 1991-06-25 The United States Of Amercia As Represented By The Administrator Of The National Aeronautics And Space Administration Horizontally rotated cell culture system with a coaxial tubular oxygenator
US5650325A (en) * 1990-11-29 1997-07-22 Spielmann; Richard Apparatus having a rotatable stack of parallel trays with culturing surfaces on opposite sides for liquid/gas exchange
US5432087A (en) * 1990-11-29 1995-07-11 Spielmann; Richard Apparatus having rotatable planar trays for culturing microorganisms
US5316945A (en) * 1991-12-14 1994-05-31 Will Minuth Cell carrier arrangement
US5427948A (en) * 1993-07-29 1995-06-27 Michigan State University Apparatus for conducting hybridization
US5403742A (en) * 1993-09-01 1995-04-04 Ramot University Authority Ltd. Bioreactor for production of products with immobilized biofilm
US5439823A (en) * 1993-09-01 1995-08-08 Martial Plant Corporation Apparatus for fast fermentation treatment
US5437998A (en) * 1993-09-09 1995-08-01 Synthecon, Inc. Gas permeable bioreactor and method of use
US6001642A (en) * 1998-06-29 1999-12-14 Wyle Laboratories, Inc. Life Sciences Bioreactor and cell culturing processes using the bioreactor
US20100290308A1 (en) * 2000-10-09 2010-11-18 Terentiev Alexandre N Systems using a levitating, rotating pumping or mixing element and related methods
US7198940B2 (en) 2000-10-25 2007-04-03 Shot Hardware Optimization Technology, Inc. Bioreactor apparatus and cell culturing system
US20090130757A1 (en) * 2005-10-26 2009-05-21 Terentiev Alexandre N Bioreactor with mixer and sparger
US20100015696A1 (en) * 2006-05-13 2010-01-21 Tom Claes Disposable bioreactor
US10632433B2 (en) * 2006-05-13 2020-04-28 Pall Life Sciences Belgium Bvba Disposable bioreactor

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Publication number Publication date
DE2341180A1 (de) 1974-03-28
DD107484A5 (US20030199744A1-20031023-C00003.png) 1974-08-05
GB1423218A (en) 1976-02-04
DE2341180B2 (de) 1975-09-25
FR2196388B1 (US20030199744A1-20031023-C00003.png) 1977-08-12
IT998367B (it) 1976-01-20
CH563456A5 (US20030199744A1-20031023-C00003.png) 1975-06-30
FR2196388A1 (US20030199744A1-20031023-C00003.png) 1974-03-15

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Effective date: 19830318